Adenovirus type 5, a member of the DNA tumor virus family, has proven to be an extremely useful model system for the study of tumor virus gene function and the regulation of cell growth. The broad, long term objective of this research program is to elucidate at the molecular level the mechanisms that underlie lytic growth and oncogenic transformation by adenovirus type 5. The specific aims of the research proposed in this renewal application are as follow: (1) Investigate the function of the adenovirus E4orf4 protein. Experiments will be performed to search for possible changes in adenovirus E1A function caused by E4orf4 protein- mediated hypophosphorylation of E1A proteins. The consequences of the interaction of the E4orf4 protein with PP2A will be ascertained, and experiments will be performed to search for interactions of the E4orf4 protein with additional cellular proteins. (2) Elucidate the mechanisms underlying function of the cellular YY1 transcription factor and the manner in which adenovirus E1A proteins alter its function. The role of YY1 at an initiator element will be further analyzed, and the mechanism by which YY1 represses transcription when its binding site is located upstream of a basal promoter will be probed. (3) Identify factor 2, a cellular protein whose DNA-binding site overlaps a YY1 binding site and is E1A-responsive. If the factor is unknown, its cDNA will be cloned, and then its normal role in transcriptional regulation and its apparent response to the adenovirus E1A proteins will be studied.